This Program Project is designed to provide funds for four projects and one core facility. The studies of the four projects will focus on the intra- and extra-cellular signals which determine the fate of lymphocytes at various stages of their life history. Particular attention will be paid to the factors which affect whether lymphocytes live or die, since the phenomena which control the proliferation and differentiation versus tolerance of lymphocytes are absolutely crucial to the health of the animal. The investigators on the first project have developed a method for isolation of very early lymphocyte progenitors. They will use these cells to find out which transcription factors they express, and how these transcription factors may affect cell development. The functions of these cells and their descendants will also be studied. The studies of the second project will deal with the effect of antigen valency on the fate of lymphocytes. The third project will concentrate on the properties of memory T cells and will study the properties which distinguish these cells from other types of T cells. The investigatory on the last project have discovered that the fate of antigen activated T cells in animals is affected by inflammatory processes. Experiments will be done to find out why antigen- activated T cells die in animals, and how inflammation prevents this death.